Renal Flashcards
GFR
the volume of fluid filtered from the kidney’s into Bowman’s space/ unit time.
filtration rate of all functioning nephrons- gives an estimation of number of working nephrons
Can be calculated by measuring the renal clearance of any stubstance that has a steady level in the blood, is freely filtered or is not reabsorbed or secreted by renal tubules.
Renal clearance
volume of plasma completely cleared of the substance/ unit time
Creatinine clearance (CrCl)
UCr/Pcr x volume/ time
creatinine is freely filtered, it is not reabsorbed by the secreted tubules. it overestimates the GFR by 15%
can be inaccurate, under collection will have a false low CrCl and over collection will have a false high
Serum Creatinine
a poor marker for renal function as it is influenced by muscle mass
Creatinine
comes from muscular creatine and phosphocreatine converted at steady rate 2% of total creatine/day to creatinine.
creatinine is released into bloodstream and excreted exclusively by the kidney’s only
Daily creatine demand meet by diatary and de novo syntheiss, plasma level is a funciton of muscle mass
Renal disease
Etiology- Rnal- Primary kidney diseases- congenital, aquired, (glomeular/ tubulointerstitial)
- Pre-Renal- inadequte blood supply- heartfailure or low cardiac output, low renal perfusion, volume depletion, Sepsis, severe bleeding
- Post Renal( Bilateral urinary obstruction
- tumors, BPH (Prostate)
Clinical manifestations- Acute nephritic syndrome- hematuria, proteinuria,
- nephrotic syndrome- proteinuria, edema, lipiduria, hypoalbuminemia, hyperlipidemia
- asymptomatic- proteinuria, anuria, azotemia
- chronic renal failure- prolonged symptoms of urema
- UTI- bacteruria, pyuria
- Nephrolithiasis- colic, hematuria
- Renal tubular defects- With polyuria, nocturia, electrolyte disorders
Nephrotic Glomerular disease
Clinical manifestations:Heavy proteinuria, oval fat bodies, free fat droplets, few cellular elements, fatty casts, edema, lipiduria
Nephritic Glomerular disease
Clinical manifestations- Red cells, Red cell casts, Granular casts, Variable proteinuria, White blood cells., hematuria, hypertension
Primary Glomerular Diseases
Morphology- neutrophils and macrophages,
Etiology- immune mediated- unkown except for infectious agents
Pathogenesis- Immune mechanisms- antibody, cell, complement. Most are immune. Antibodies may be formed in response to endogenous antigens such as from tumor antigens or kidney antigens. they can also be formed in response to exogenous antigens such as drugs or organisms (viral or fungal). antibodies combine with antigen in periphery or insitu forming an immune complex. the immune complex formed is localized in various parts of glomerulus, this can activate the compliment and inflammatory cells. This causes injury to glomerular filtration membrane(AND)
- Non immune mechanisms- reduction of renal mass
Immune mechanisms for primary Glomerular disase
Insitu immune complex- Ag-Ab formation, fixed antigens for anti GBM (nephritis. Planted antigens(exogenous or endogenous
Circulating immune complex- endogenous antigens for DNA or exogenous antigens for infectious protein
Cytotoxic antibodies-
direct cell injury, without immune complex deposits.
cell mediated- Sensitized T cells will cause Glomeruluar injury
Activation of alternative complement- polysaccharide, endotoxin, IgA aggregates activates C3 which activates C3bBb
Non- immune mechanisms for Primary Glomerular disease
this is caused by Focal Glomeruloscerosis which. It will lead to systemic hypertension, intraglomerular hypertension, glomerular hypertorphy, these lead to mesangial cell hyperplasia/ECM deposition, intraglomerular coagulation and epithelila injury, this causes Proteinuria and Focal glomeruloscerosis.
Histological alterations of the glomeruli
diffuse- all glomeruli,
Focal- some glomeruli
global- entire glomerulus
Segmental- part of the glomerulus.
Immunofluorescence : stais for IgG IgA IgM C3 Kappa, Lambda
distribution can be along the GBM, Mesangium or both and can be patchy or diffuse, with a fine or courase grnular or lienar pattern.
Reasons not to perfomr a Kidney Biopsy
Advanced renal disase with small, echogenic kidneys or ultrasound, patient is a young child with nephrotic syndrome, clinical picture and associated systmeic findings are fairly definitive. Orthostatic proteinuria, Normal complement, normal creatinine, normal blood pressure and limited proteinuria.
Nephrotic Syndrome
Lab findings:Heavy proteinuria, hypoalbuminemia, edema, hyperlipidemia and lipiduria, NORMAL complement
Etiology: Glomerular damage causes increased permeability of glmerular capillaries to protein, this causes albumin to leave and other proteins. This will decrease the plasma oncotic pressure which causes edema, it also decreases PLASMA VOLUME, GFR, ALODSTERONE SECRETION, this causes fluid retention and edema
- hypoalbuminemia also causes compensatory synthesis of proteins by the liver which also includes lipoprotien which will cause hyperlipidemia
Pathogenesis- Immunoglobulin deposition causes membranous nephropathy
- non immunoglobulin deposition causes minimal change, FSGS, diabetic nephropathy, amyloidosis
Minimal Change disases
Epidemiology: most common disorder in children, in 15% of adults
morphology: LM- normal glomeruli, tubules, vessels
IF- no deposits
EM**** Fusion of foot processes and efacement, detachment of basement membrane
Etiology- Idoiopathic usually, may be lymphoma or renal cell carcinoma
Pathogenesis: Primary target is glomerular epithelial cells (Podocyte) results in increased glomerular permeability and subsequent massive proteinuria. NO IC deposition, non inflammotry. it is unclear but may involve ciculating glomerular permeability factors. This is because people who have transplant have recurrence of FGSG or minimal change disease
clincal features
Course:90% will have complete remission of proteinuria within 8 weeks of steroids but with frequent relapses, children 1/3 no relapse, 1/3 relapse few times, 1/3 relapse frequently
-in adults, remission and relpases
-renal failure and mortality rates are low but higher in adults.
- die to complications of Nephrotic Syndrome or therapy
Complications: tendency to progress into CRF/ESRD
Lab diagnositcs: low serum albumin, normal serum creatinine,
- Urine: proteinuria, bland urine sediment,
- normal BP, Edema (periorbital and pedal)
FSGS
Epidemiology- 10-15% idiopathic nephrotic syndrome in children, higher in adults
MorphologyLM- FSGS
IF- negative or non specific granular deposits of IgM or C3
EM- patchy fusion of the foot processes and effacement
Etiology: often idiopathic
-secondary to HIV, Morbid obesity, chronic reflux renal ablation nephropathy, heroin use, malignancies(lymphoma), glomerulonephritis, Congenital unilateral renal agenesis or aplasia
Pathogenesis- secondary- reduction in renal mass due to any renal disease, glomerular or other causes compensatory hypertrophy and hyperfiltration of remaining glomeruli to maintain FGR, intraglomerular hypertension, Hyperfiltration injury this causes Gllomerulosclerosis
Clincal features:- Present with nrephrotic syndrome: insidious onset of asymptomatic proteinuria
Course: degree of proteinuria is improtant for prognosis. persistent proteinuria and progressive decline in renal function. ESRD -5-20 years. with 50% recurrence post transplant. IgA nephropathy
Associations:Hypertension, renal insufficiency
complications:Progression to nephrotic syndrome, massive proteinuria, microscopic hematuria,
Membranous nephropathy
Morphology-LM: diffuse thickening of GBM, little increases in cellularity
- IF: fine granular deposits of IgG, C3 along the basement membrane-subepithelial
- EM- subepithelial immune complex deposits and proliferation and growth of new GBM spikes formation
Pathogenesis: localization of IC in sub epithelial zone as a result of formation IN SITU or CIRCULATIONG IC, Resembles Heymann Nephritis. (subepithelial localization) C5b-C9 insertion into podocyte cell membrane causes damaged GFM, increased permeability massive protein uria
Clinical features- Nephrotic syndrome, Microscopic hematuria (50%), Hypertension, Renal insufficiency(late), renal vein thrombosis
Associations(antigens and disorders) Idiopathic, endogenous antigens (DNA SLE/tumors) exogenous antigens,
-hep B, syphilis, malaria, captopril, mercury, gold, penicillamine
Course: 20 year follow up 25% have remission, 50% persistent proteinuria and stable or only loss of renal function 25% develop ESRD, poor prognosis for male, over 50, and greater than 10gm of proteinuria.
Heymann nephritis
animal model of human membranous nephropathy
-mice immunized with a renal apithelial antigen that develop autoantibodies IgG cross GBMs and bind to antigens on visceral epithelial cells (podocytes. the HNAC (resultant immune complex is shed into adjacent subepithelial space and produce pathological features
Diabetic nephropathy
epidemiology: leading cause of end stage renal diseases in USA 25-40% of type 1 and type 2 diabetics
Morphology- early lesions- expansion of mesangial matrix and thickening of GBM
- later lesions- diffuse glomerulosclerosis with diffuse increase in measangial matrix and diffuse thickening of GBM
- Kimmelstiel Wilson nodules. (contain lipids and fibrin
- fibrin cap and capsular drop(plasma proteins
- ischemia: causes tubular atrophy, interstitial fibrosis and hyaline ateriolsclerosis.
Etiology: adverse effects of systemic hyperglycemia
pathogenesis: hyperglycemia causes non-enzymatic glycosalation, advanced glycosylation products, increased growth factors (TGFbeta), activation of cytokines and formation of reactive O2 species. These leads to
- increased matrix formation and mesangium expansion
- increased type IV collagen, fibronectin and decreased proteoglycan heparin sulfate with thickening of GBM,
- hemodynamic changes- hyperfiltration, increased glomerular cappilary pressure, glomerular hypertrophy
- these all lead to glomerulosclerosis.
clinical presenation: nephrotic syndrome:
course: increased glomerular hydrostatic pressure, after 7-13 years, incipient nephropathy, after 10-20 years, macroalbuminuria, overt nephropathy
20+ years, presistent and progressive HTN, highly variable decline in FGR from 1-24 ml/min/year
Amyloidosis
Morphology: LM: nodular, amorphous hyaline material in the mesangiu and capillary loops, with resultant narrowing or closing of capillary lumens. IM: Congo red stain positive with apple green birefringence
EM:subendothelial and mesangial fibrils.
Etiology: deposition of amyloid fibrils that are composed of soluble proteins that have undergone misfolding resulting in formation of b-pleated sheet structrues,
-no immune or inflammatory response, damage and dysfucntion due to infilatration by amyloid fibrils and replacement of normal organ architecture with consequent loss of cellularity.
Pathogenesis: beta pleated sheets autoaggregate to from aggregates which are sistant to catabolism and removal.
- AL primary- light chain or fragment of light chain produced by abnormal plasma cells (fibrils compsoed of light chains)
- AA secondary amyloid, amyloid precursor protein is an apolipoproteind produced by the liver as an acute phase reactant in response to LONG STANDING INFECTION OR INFLAMMATION>
Clinical features- proteinurai, edema, nephrotic syndrome. Renal insufficiency , fanconi’s synrome(electrolyte abnormal)
- CVS: CM/CHF, arrythmias, heart block,
- GIT: hepatomegaly, malabsorption, bleeding,
- Neuro: ischemic stroke, neuropathy, orthostatic hypotension,
- skin: easy bruising and purpura.
Diagonsis- biopsy of organ involved
Course-Very poor, many die of end organ failure
Association- multiple myeloma(primary)
- rheumatoid arthritis, Behcet syndrome, crohn’s disease, Osteomyelitis, Tuberculosis, renal Cell carcinoma, Hodgkin’s disease. congestive heart failure
Nephtritic Syndrome
Morphology- Urine Sediment- Red blood cells and Red blood cell casts.
- granular casts
- variable proteinuria
-possibly WBC
Normal complement levels
- IgA nephropathy- Henoch-Chnolein Purpura, Alport’s syndrome (hereditary nephtritis, SLE- Class I, II, B, Benign Hematuray
IgA nephropathy
epidemiology: Most common type of glomerulonephritis, any age, peak in 2nd and 3rd decades, Asians, caucasians, rare in blacks
Morphology- LM segmental areas of increased mesangial matrix and hypercellularity
IF: Mesangial and subendothelial deposits of IgA and C3( +/- IgG, IgM
EM: mesangial and subendothelial deposits
Pathogenesis- Production of IgA class Ic mainly from mucosal immune system. supported by clinical hematuria worsens during URI or GI infections, has a predilection for mesangium. (depositions.
clinical- eipsodes of gross hematuria, persistent microscopic hematuria between episodes. non nephrotic proteinuria normal C3C4
Course- generally prolonged benign, 20% wil progres to ESRD. most restricted to kidney but can be assocated ith others
Associations- viral respiratory illness or GI illness, arthritis, vasculitis, non-thrombocytopenic purpura (HSP), hepatic Cirrrhosis, Gluten enteropathy, HIV infection. Minimal change, Membranous wegener’s, ankylosing spondylitis, small cell Carcinoma.
Post streptococcal Glomerulonephritis
Epidemiology- More common in children 6-10 years old
Morphology: LM- hypercellular glomeruli,(neutrophils and monocytes. Proliferation of mesnagial and endothelial, epithelal cells, profess is Diffuse, closure of capillary loops due to proliferationand swelling of endothelial cells and leukocytes infiltration.
IF- granular deposits of IgG and C3 in mesangium and along capillary walls
EM- electron dense deposits in sub epithelial space humps
Etiology- nephritogenic strain of b-hemolytic streptococci
Pathogenesis- usually 10 days folloing pharyngitis or 3 weeks following impetigo. due to late period of antibody formation. intially subendothelial IC depositis that causes activation of complement and influx of inflammatory cells with resultant prolifererative GN decline in GFR, Depsoits are rapidaly cleared accounting for resolution of hematuria and renal faiulre.
- later- characterisitc subepithelial HUMPS responsible for epithelial cell damage and proteinuria
- IC deposits cleared slowly and are separated from circulation by GMP limiting their clearance. This accounts for the slow rate of resolution of proteinuria.
Clinical features- Proteinuria more than 2gm/ day. Complement levels always low. .
Course: lesions begin to resolve after a month or two and usually completley rsolved over 9 months to several years. in children almost always renal function recovered (less than 1% irrevirseble renal faiulre
- long term prognosis, some develop renal insufficiency after 10-4 years after initial illnees.
- some glomeruli irreversibly damaged, results in compensatory hypefiltration in remaining glomeruli to maintain normal fGR
- Long standing increased glomerular capillary pressure eventualy results in hemodynamic mediated injury and glomerulosclerosis
diagnosis: history, clinical presentation. elevated titers for antisterptolysinO Ab or anti DNAase B, in assocation with low complement, no renal biopsy because usually gone
Membranoproliferative glomerulonephritis (MPGN)
Morphology- thickening of the basement membrane, mesangial proliferation, infiltration of inflammatory cells.
-LM- mesangial expansion and hypercellularity, thickening of capillary loops due to double countour formation “tram track” which is duplication of GBM
-EM Type 1: Subendothelial deposits( C3+ IgG)
Type 2 deposition of dense material along GBM- unknown composition (C3)
Type 3: Subendothelial, mesangial, subepithelial deposits. C3-IgG
Etiology- primary is idiopathic, secondary is underlying systemic disorder
-Type 1 most common, idiopathic is rare, secondary forms more common- Lupus, hep C, cryoglobuilnemia, endocarditis, parasitic infection.
Pathogenesis- Type 1 complement classical activation.
Type 2 alternate complement pathway. C4 levels may be nomal but C3 remains depressed for prolonge periods due to C3 nephritic factor. (IgG binds to and stabilizes C3bBb convertase which casues continuous degradation of C3
clinical- usually before age 30 shows, hematuria or proteinuria in urinalysis, acute nephritic syndrome with hematuria, hypertension and edema, recurrent episodes of gross heamturis, insideious onset of edema and nephrotic syndrome.
course: most progress towards ESRD within 10-15 years.
Rapidly progressive Glomerulonephritis (RPGN)/ Crescentic glomerulonephritis
Morphology:LM- proliferative GN with prominent Crescent formation and segmental necrosis, crescents evolve from ceullular or fibrocellular to fibrous cresecents (fibrous is irreversible.
IF: Type 1- linear staining, anti GBM disease, Goodpasture’s syndrome idiopathic
-Type 2- Granular staining- immune complex disease- SLE, post infection, IgA, henoch Schonlein (HSP), idiopathic,
Type 3 No Staining- Pauci immune GN, Wegener’s, microscopic PAN, Church strauss, Idiopathic,
rapid decline in renal fucntion with severe oliguria, three types 123, Severe glomerular injury
-proteinuria, hematuria, red blood cell casts, hypertension, edema, variable degree of oliguria
Course: 75% die or placed on dialysis, best prognosis with treatable underlying disorder or one that spontaneously remits. (post strep)
diagnosis: renal biopsy, serology needed for diagnosis
Serology- ANCA+- no extra renal disease= idiopathcicrescentric GN, Systemic necrotisizng arteritis = Microscopic polyarteritis nodosa, Pulmonary necrotizing granuloma= Wegener’s
-Anti GBM+- if lung hemorrhage= good pastures if no anti GBM
- immune complex- Anti DNA ab= SLE, Anti strep=post strep, cryoglobulins= Cryoglobulinemia
Lupus nephirits
Epidemiology- 25-50 have renal disease onset, 60% of adults with SLE develop renal disease
Morphology: type 1- minimal mesangial LM-normal, IF and EM, mesangial immune deposits.
-Type 2 mesangila proliferative- expansion and hyperceulluarity, show, is mild,
-Type 3 focal segmental proliferative LM: less than 50% glomeruli affected on Lm subendothelial and mesangial IC deposits, complement activation and influx of inflammatory cells,
-Type 4-diffuse proliferative-moe than 50% glomeruli affected on LM, marked deposition of IC subendothelial and mesangium, crescents and necrotizing lesions.
-Type 5 membranous- subepithelial immune complex deposits, diffuse thickening of GM.
Type 6 advanced sclerosing lupus nephritis- End stage. Global sclerosis in more than 905 of glomeruli, advanced interstitial fibrosis and tubular atrophy, represents healing of prior inflammatory inury and advanced stages of chronic 3, 4, 5 lupus
etiology- atuoimmune disorder of uknown etiology, , production of autoantibody with immune complex formation that may lead to chronic inflammation and tissue distruction in a variety fo organ systems .
pathogenesis: abnormal production of antibdoies for endogenous nuclear antigens (dsDNA, ANA, sm, RNA, Ro, La- immune complex is deposited in kidney with complement activation and recrutiment of inflammatory cells and tissue destruciton.
clinical features: 90% joints, 70% skin rashes, 30% discoid lesions, 40% alopecia, 60% pleura-pericardium, 50% kidney, Raynauds -20%, Mucus membrane- 15%
CNS-15%
Type2- mild, microscopic hematuria, proteinuria, nephrotic syndrome, Renal insufficiency rare.
Type 3- heamturia, nephrotic syndrome, hypertension, renal failure
type 4- Diffuse proliferative lupus nephritis- most comon and most severe,: hematuria, proteinuria, nephrotic syndrome, renal failure, low complements, high anti-DNA levels.
Type 5- nephrotic syndrome, bland urine sediment, mild renal insufficiency, normal C3C4 negative anti DNa, Ic deposits in blood vessles.
diagnosis: more than for of the following
- malar rash, discoid rash, photosensitivity, oral ulcers, non erosive arthritis, pleuropericarditis, renal disaes, neurological disorder-schizophreina/ psycchosis, hemotological disorder (Hemolytic anemia, LwWBC Lw PLT), postive LE prep, anti dsDNA ab, anti Sm, False positive for anti treponemal test, positive fluorescent antinuclear antibody test.
Benign Hypertensive nephrosclerosis:
Clinical features: Hypertension (25% ESRD)Benign as pateients are asymptomatic usually normal or slight reduced FGR
Risk factors for ESRD- Blacks, Higher blood pressure, second underlying CKD (diabetes)
Pathogenesis: Vascular: medial and intimal thickening, which is response to hemodynamic changes, hyaline arteriosclerosis due to extravasation of plasma proteins through injured endothelium
Glomerular- Global sclerosis (ischemic injury leading to nephron loss) FSGS an adaptive injury, compensatory hyperfiltration due to nephron loss,
-Tubules and insterstitium- Tubular atrophy and interstitial fibrosis. (ischemic mediated.
clinical presentation- histor of HTN, progressive elevation in serum creatinine, mild proteinuria of less than 1 g/day, no microscopic hematuria, few progressing to ESRD
Diagnosis- long standing hypertension, gland urine sediment with MILD proteinuria, Left ventricular hypertrophy, retinopathy, stroke.
Malignant hypertensive nephrosclerosis
renal disease associatied with marked increases in blood pressure generally greater than 180/120 (diastolic more than 130, most common in young black males.
etiology- preexisting essential hypertension, secondary hypertension (pheochromocytoma, primary hyperaldosteronism,)
pathogenesis: sever ehypertension leads to endothelial wall injury in arterioles and capillaries, this will cause fibrinogen, platelet deposition, plasma proteins, which causes fibrinoid necrosis and intravascular thrombosis.
Crisis- renal failure(marked proteinuria, microscopic gross heamturia, elevated creatinine, ARF) and other organs inolved, brain(nausea and vomiting, headache, encephalopathy, stroke, seizures), eye(blurry vision, loss of vision. , heart(Acute MI, Aoritc dissecion lungs(Pulmonary edema), large vessels, organ damage over hours to days. medical emergency need intravenous antihypertensive medications to avoid irreversible damage,
Thrombotic microantiopahties
HUs and TTP
HUS/TTP
Morphology-
etiology
Pathogenesis:abnormal platelet aggregation leading to thrombsis in arteriorles and capillaries throughout the body. Thrombosis in small vessels results in mechanical injury to circulating RBCs,
Clinical microvascular thrombi lead to ischemic injury to target organs in kidney brain and heart
Clinical ground and lab findings. microangiopathic hemolytic anemia, chistocytes in peripheral blood smear, thrombocytopenia, purpuric rash, acute renal failure, neurological abnormalities, headache, confusion, seizure stroke, fever.
HUS:seen in chldren one week after episode of bloody diarrhea caused by enterohemorrhagic E coli- more severe renal failure less pronounced CNS.
associated with viral infections, shigella, slamonella, drug induced with quinine, gemcitabine, cyclosporine, ticlopidine, oral contraceptives.
TTP- CNS invlovement more pronounced, renal failure less severe, assocaited with SLE, HI, Hemotalogical malignancy
Renal artery stenosis.
Etiology: Narrowing of one or both of the renal arteries, 75-90% due to occlusion by athermatous plaque, 15-25% fibromuscular dysplasia, also Takauyasu’s arteririts, aortic/renal artery dissection. prevalence increases with age.
Morphology-(ischemic nephropathy) diffuse ischemic atrophy in kidney, crowded glmeruli, atrophic tubules, interstital fibrosis, no significant arteriolosclerosis in kidney of affected RA stenosis, Arterioles protected from transmission of high pressure due to stenotic renal artery, hypertensive arteriosclerosis in contralateral kidney due to increased systemic pressure.
Diagonsis- onset of HTN in less than 35 or greater than 55, sudden onset of unctrolled HTN in previously well controlled patient, accelerated malignant hypertensions, intermittent pulmonary edema wiht normal LV function (flash pulmonary edema, acute pulmonary venous congestion or volume overload)
Labs- flank or epigastric bruit, ARF
- asymmetrical kindy sze, Renal artery doppler measurement of blood flow velocites in renal arterites to aorta is more than 3.5 MRA renal arteries, anatomical, CT angiogram: anatomical Renal arteriogram- gold standard.
-use an angioplasty and stent if you have uncontrolled hypertension, declining renal funciton and recurrent pulmonary edema.
ATN Acute tubular necrosis
Acute injury to renal tubules, causing death(necrosis) and acute renal failure
Etiology- ischemic and toxic. ARF intrinsic and pre-renal cause-
Clinical symptoms- (36 hours initiation phase) acute decline in GFR, Oliguria/anuria, serum BUN and creatinine increased
-maintenance phase- plateau of serum creatinine and BUN- lasts for days to 3 weeks(oliguria, Uremic symptoms, fluid overload, metabolic acidosis, hyperkalemia, dialysis
-recovery phase- Tubular function is restored, Increased GFR, increase urine volume, Gradual decrease in creatinine and BUN
Clinical findings- Elevated serum creatinine and BUN, metabolic acidosis, hyperkalemia, hyperphosphatemia, anemia(decrease in erythropoietin.), Hypotension, low urine output(oliguria,anuria), pericardial friction rub confusion(uremic signs)
-inschemic insult- hypotension, vasodialotry septic shock with systemic infection, - hemorrhagic shock due to gastrointestinal bleeding, hypovolemic shock due to vomiting and diarrhea
Diagnosis- muddy brown granular casts, epithelial cell casts, free epithelial cells, proteinuria, microscopic hematuria, no pyuria, urine may be normal in severe disease.
Nephorotxic- exogenous aminoglycodsides, contrast media (CT/cardiac cath) endogenous, with hemoglobinuria, myoglobinuria
Tubulo interstitial nephritis
group of disases characterized by interstitial inflammation, edema, fibrosis and normal glomeruli
- impaired urinary concentration 9polyruia, nocturia)
- salt wasting- hyponatremia
- metabolic acidosis- decrease ability to excrete acid
- no significant protenuira or hematuria
etiology: Acute: drugs, infection, idiopathic, sarcoidosis
- chronic- infection, pyelonephritis, analgesic abuse, ASA, tylenol, urate nephropathy
Acute drug induced interstitial nephritis (AIN)
Morphology- urine microscopy, eosinophils, sterile pyuria, WBC casts, proteinuria,
Blood tests, increased BUN and creatinine, increased eosinopihls count, tubular dysfunction so high K and low HCO3
Etiology:Penicillins, sephalosporins, NSAIDS, Sulfonamids, Bactrim, furosemide, thiazide, diuretics, ciproflaxacin, rifampin, cimetidine, allopurinol, proton pump inhibitos, omeprazole, lansoprazole.
Pathogenesis- allergic type reaction manifested by interstitial infiltration of eosinophils, lymphocytes and macrophages.
Clinical presentation- 2 week onset after start of meds. or 2-5 days if second exposure to drugs, Fever, rash, eosinophilia, Traid of all, or ARF, oliguria, asympotmatic.
course, if you stop the drug and use oral steroids to help recovery you can have a complete recovery or incomplete with persistent elevation of creatinine.
Acute pyelonephritis
Etiology- Bacterial endocarditis, septicemia, UTI
pathgenesis- infection enters through the blood stream seeding the kidney from a distant source or ascending infection from the lower urinary tract
Ascending infection
-women bacterial colonization of introitus and distal urethra, entry into the bladder, due to short urethra, foley’s catheter, sexual intercours.
-men entry into the bladder, BPH, catheter, urine stasis, bacterial colonization, bacteria travel retrograde up the ureters to the kidneys (Vesicoureteral refulx)
Clinical features: Fever, dysuria, flank pain, nausea, vomiting, costovertebral angle, tenderness, elevated BUN, creatinine, elevated WBC, pyuria, bacterurai, WBC casts.
complications: papillary necrosis, pyonephrosis, perinehpric abscess
Chronic pyelonephritis
recurrent or persistent renal infection, chronic tubulointerstitial nephritis,
2 forms, Chronic obstructive and reflux
Morphology- Chronic obstructive happens in the posterior urethral valves, with kidney stones. gross you will see diffuse dilatation of calyces and scarring, Microscopic you will see tubular arophy, chronic interstital inflammation, fibrosis in cortex and medulla FSGS
- Reflux happens because of vesicoureteral reflux, will show preferential scarry and calyceal dilation at the poles,
Etiology- Phenacetin, ASA, caggeine, Acetaminophen, odeine, ingestion of large quantities, papillary damage due to direct toxic effect or ischemic effect of ASA, Chronic tubulointerstitial nephritis, excretion of necrotic papilla gross hematuria and renal colic.
Clinical features- refulx is silent, onset, with late presentation in course of disease- will show renal insufficiency, hypertension, proteinuria, significant with FSGS
Course- Progressive renal failure or urothelial carcinoma
- uncommon but serious, interstitial inflammation compress medullary vasculature leading to ichemia and papillary necrosis.
Associations progressive renal scarring, decline renal function and end stage renal disease, patients with anatomical abnormalities
Obstructive Uropathy
Obstruction at any level of urinary tract from urethra to renal pelvis, obstruction above the bladder can be unilateral or bilateral
Etiology- BPH, Bladder cancer, kidney stone, retroperitoneal adenopathy, papillary necrosis (sloughed papillae)
Course as a resulted of the glomerular fiatration but inabilty to excrete, it diffuses back in to the renal intersittium, there will be high pressure in the pelvis which is transmitted through the collecting tubules into the renal cortex causing renal atrophy, renal function fully recovered if relieved fast. irreversible damage and renal failure if obstruction not relieved by 2-3 weeks
association with hydronephrosis
Renal stone disease, nephrolithiasis/urolithiasis
Epidemiology- common- 5-10% of americans, peak onset at 20-30 years, men more.
Etiology: idiopathic or specific disease like gout, cystinuria, hyperoxaluria
Morphology- mot common calcium oxalate and calcium phosphate, made of struvite, uric acid and cystine as well.
Clincal symptoms- silent if they remain in pelvis, symptomaitc if the stone passes into ureters,
- renal colic, abrupt onset of flank pain radiating to groin, nausea, vomiting, gross or mircorscopi hematuria, ulceration or urothelium
- superimposed UTI, urinary stasis, trauma
- hydronephrosis due to obstruction of ureter.
treatement- antibiotics, urological intervention or surgery(laser surgery to break it up or resection)
prevention- decrease of urinary concentraiton of causing substances, increased fluid intake , low sodium diet, decrease urinary calcium excretion CA reabsorbed in in PCT with sodium alkalinization of urine to increse, solubility of uric acid.
Cystic Kidney disease
Etiology
-Genetic- adult autosomal dominant polycystic kidney disease, autosomal recessive childhood polycsytic kidney desiease
Aquired- benign simple cysts, medulllary sponge kidney
Cysts- associated with systemic diseasesVon hippel lindau syndrome (VLHS0
tuberous sclerosis
Adult dominant polycystic kidney disease
Morphology- multiple fluid filled cysts leading to increased kidney size
Etiology abnormal chormosome 16p13.3 PKD1 gene or abnormal chromosome 4q21 PKD2 gene which is milder, later onset, fewer smallcysts, and slower progression with later ESRD
Pathogenesis- altered tubular epithelial growth and differenation. growth of cysts leads to compression and destruciton of normal adjacent parenchyma, glomerulir are overperfused. but only a small number of nephrons invovled with no evidence of FSGS. Renal biopsy shows arteriolar sclerosis and interstitial fibrosis.
Course- increases in size and number with age, and they arise in different areas of tubule.s
clincally- often silent 50% of cases will be diagnosed during patient lifetime, but accounts for 4-6% of ESRD
- hypertension due to cysts compresiosn of renla vessels which increases renin and aldosterone
- hematuria- rupture of cysts in collecting system,
- flank pain- stretching of renal capsule
- nephrolithiasis- uirc stones, calcium oxalate.
assocations- extra renal mainfestations- hepatic cysts, cerebral aneurysms, pancreatic cysts, cardiac valve disaese (MVP, AR) colonic diverticular disease, abdominal wall and inguinal hernia. the prevalence increass with age and 80% over age 30, usually asymptomatic and mild synthetic liver funcion intact, may cause pain due to distension on liver capsule.
Childhood polycystic kidney
Etiology- Genetic- Gene PKHD1 on chromosome 6p21-23
Morphology- enlarged cystic kidneys at birth, cysts arising from collecting ducts, hepatic fibrosis, and
typical outcome is variable from death in infancy to childhood.
Simple renla cysts
can be single or multiple. do not predispose to CRF or cancer, and more common with older age.
Alport’s syndrome
Morphology:
- LM: caration of the thickness of the BM and GFSGS
- IF: negative and negative with segmental stain for alhpa 3,4,5 collagen GBM
- EM- Thin BM, splitting and lamination
Etiology- efect in collagen IV synthesis in the bsement membrane
- mutations in COL4A4 and COL4A5 genes
- Xlinked but have AR and AD
Clinical features- 5-20 years old, males more than females, nerve deafness, nephritis (hematuria, proteinuria, renal failure, ) eye disorders (Juevinle form) hematologic disorders are rare (thrombocytopenia.
Renal cortical papillary adenoma
Autopsy series
Pathology “safe Criteria” is less than 5 mm in size
Morphology: tubulopapillary/papillary basophil cell type, no clear cells
angiomyolipoma
benign tumor that is rarely malignant
involves the lymph nodes, spleen, renal vein, but not malignant,
Etiology- 50% due to tuberous sclerosis, asymptomatic, and small
Clincal features- 45 years old with flank pain, mass, hematuria, retroperitoneal hemorrhage, triphasic, Muscle, fat, vessels)
Renal cell carcinoma
Epidemiology- most common cancer of kindey(90%) peaks in six decade of life, males more than females.
Morpholgoy: majority are sporadic, unilateral, and single,
Etiology: malignant tumor of renal tubular epithelial cells 5% genetic, ( AD RCCA, Von-Hippel-Lindau BHL disese, Hereditary papillary RCCA (multiple bilateral younger age group))
Clinical- hematuria(most common sign), flank pain, palpable mass in less than 10% of patients, frequently asymptomatic and there is incidental imagin,
PARANEOPLASITC SYNDROME- polycythemia(erythropoeitin), Hypertension(renin) hypercalcemia (PTH), Cushing’s syndrome(ACTH), Leukemoid reaction, Amyloidosis.
Investigations: Renal ultrasound, CT scarn, IV pyelograph, biopsy, Urine Cytology is not good.
Staging: 1 confined to kidney and less than 7 cm- 5 years (60-80 %
2- confined to kidney 7-10 cm- 5 years (40-70 %
3 invasion of renal sinus or pernephritic fat, grossly invades renal vein or muscle containing branches, b. invasion of vena cava or c.vencava wall- 5 years 10-40%
4- invasion of adrenal gland or beyond gerota’s fascia. 5 years (5 %)
Treatment is nephrectomy
Wilm’s tumor
Epidemiologycommonst solid tumor in children under 6 years
Morphology- single well circumscribed, encapsulated soft, fleshy grey white tan. Gross examination is critcal staging,
Triphasic pattern, Blastema, stroma, epithelial, anaplasia
Etiology- cytogenic- 2 tumor suppressor genes short arm of chromosome 11
Urethelial carcinoma
Epidemiology: mean age 50-80 years, male more than females,
Morphology: Flat Lesion: noninvasive/invasive, papillary lesion, Noninvasive invasive.
etiology: mutations of p53, Rb, p15 genes
risk factors: smoking is greatest (2x), analgesic abuse phenacetin, cyclophosphamide, chemical workplaces like naphtylamine, rubber products, infections-schistosomiasis.
clinical features: painless hematuria, dysura, urgency and frequency, flank pain, metastatic disease in up to 50%
Course- prognostic factors- depth of invasion, nodal metastases, distant metastases, Grade based on low or high grade.
Stage A- invasion of lamina propria.
-Stage B- invasion of superficial or deep detrusor muscle
-Stage c- invasion of the paravesical tissue,
-Stae D- metastases to organs or tissues in regional lymph nodes or distant site.s.
- Survival 98% 10 years in low grade, 40% 10 years in high grade, 20% 5 year with deeply invasive with a 57% overall survival rate.
treatement- ca in situ- TUR, chemo.
- noninvasive papillary- TUR
- invasive Ca- TUR, superficial, cystectomy with deep, radiotherapy,
- metastatic- chemotherapy
Ureithelial papilloma
benign tumor, rare
urethelial papillary carcinoma
75% of all bladder tumor, exophytic tumor, low grade, superficial invasion, multiple recurrence, Multifocal, tumor progression in 5-10% which are high grade.
Urethelial flat carcinoma
deeply invasice carcinoma at diagnosis, infrequently papillary in 10%, usualy a high grade tumor, metastases to regional nodes, liver, lung, bone, poor prognosis.
Urethelial squamous cell carcinoma
Etiology: 5% of primary carcinoma, schistosoma hepatobium
course: worse prognosis.
has to have no element of urethelial carcinoma.
Diverticula
Etiotlogy- congenital due to defect in development of the muscle wall of bladder, aquired is due to increase in intravesical pressure secondary to obstruction of urine outflow.
Complications- urine stasis, infection, stone formation, carcinomas.
Urachus
persisitent tubular structure, bladder dome to umbilicus, cystic- draining sinus, carcinmoa, surgical excision.
Cystitis
Etiology- usually a secondary infection to
- Baceteria- E.coli, Progeus, Klebsiella, enterobacter,
- Fungus- Candida
- parasites- schistosoma hematobium
- iatrogenic- chemotherapy, radiation(hemorrhagic cystitis
- risk factors- more common in female, diabetes mellitus, instrumentation, bladder calculi, baldder outlet obstruction.
Pathogenesis
Clinical features- urinary frequency, dysruia, pain or burning micturition, pain over bladder/suprapubic , fever and chills, microhematuria.
Uruothelial adenocarcinoma
2% pirmary, 50% urachal origin
Chronic interstitial cystitis
Unknoen etiology, middle age female,
clincally: suprabutic pain, frequency and urgency, nocturia/ hematurai,
Edema, homrrhage ulceration, chronic inflammation, mast cells
Prostatitis
Cllinical- dysuria, frequency, urgency, low back/ pelvic or genital pain. Fever, Chills and leukocytosis, loss of sex drive, painful erections/ejaculation. DRE- enlarged tender prostate.
Benign prostate hyperplasia (BPH)
Pathogenesis-might be hormone dependent, the testosterone with the 5 alpha reductase type 2 and in the stromal cells and epithelial celsl tand they produce growhth factor that causes proliferation. there are increased receptors for testosterone.
BPH is common in old age when testosterone levels are low, treatment with testosterone doesn’t aggravate BPH, possible role of estrogen- increased receptors for DHT on prostatic cells
Clinical- urethral compression, difficulty starting and stopping urination, frequency, dribbling, nocturia, dysuria, Urine retention due to inability to completely empty the bladder
complications- infection, obstruction. Not premaignant. Treatement- TURP, transurethral resection- 5 alpha reductase inhibitors- fenastiride.
Prostate Carcinoma
Most common cancer in Men in USA, 2nd most common cause of cancer related to deaths in men over 50 years
Risk factors- greater than 65, african, caribbean africa, low in asians, high fat diet, family history. hereditary forms in 9% of all cases and up to 40% of early onset disease hereditary prostate cancer gene(HPC1) linked in prostate cancer families in the RNASEL GENE
clincal features- asymptomatic-50%, hematuria, bone pain(usually back pain in late stage/metastasis) weight loss, nodular hyperplasia, dysuria, weak interrupted urine flow.
course- screening of men over age 50- PSA screening, DRE(70% are in the peripheral zone and easily palpable), transurethral Ultrasound(evaluation for abnormal DRE or PSE and possible biopsies. (6-12 biopsies from multiple ares- right and left lobe apex, base, mid, zone, transition zone.
Staging. Stage 2a. one half of one lobe or less, b. more than one half but not both, c. invlved both loves.
Stage 3 a. extraprostatic extension, includes microscopic involvement of smooth muscle at bladder neck b. invasion of seminal vesicle,
Stage 4 tumor is fixced or invades adjacent structure other than seminal vesical
early- 5 year survival 80%
advanced 5 year 20%
-radical prostatectomy radiotherapy, hormonal therapy, cryosurgery.
PSA
produced by prostatic glandular epithelium, functions on seminal liquefaction, PSA is produced in larger quantities by malignant cells.
-occurs in both free and bound forms(alpha 1 antichymotrypsin and alpha 2 macroglobulin) both are measured.
- higher the level the more likely but gray area between 4-10 ng/ml. don’t provide diagnosis,
can be high in cancer, BPH, prostatitis, infarcion, ejaculation, extensive exercise, biopsy, cytoscopy, dRE.
- free PSA- in the fray area a low percent of fPSA of less than 10% = risk of prostate cancer by 50% biopsy would be recommended.
PSA density
ratio of serum PSA to the volume of the prostate as determined by TRUS, if greater than .125 it is 80% likelihood of detecting cancer, not as accurate as fPSA
PSA velocity
change in serum PSA over time. requires serial sampling there is a high degree of suspicion when the serum PSA increases more than .75 ng/ml/year
Gleason grading.
relates to prognosis- 5 grades, with grade1 is well differentiated and 5 is poorly.
select the most predominant pattern, grade each of them grade 1-5 add the two numeric figures, less than 4/10 is good prognosis, 5-7/10 intermediate, more than 8/10 = bad prognosis.
Cryptorchidism
more common on right side, majority unilateral, 25% bilateral. more common in preamutre
Etiology can be because of anatomical anamolies, hormonal dysfunction.
mechanical
complications- 35X germ cell tumors, intraabdominal infertility. orchiopexy before age 5 y tumors, orchiopexy before age 2 y infertility.
Epididyomoorchiits
etiology varis with age- children- gram negative bacilli less than 35 years - STD- gonorrhea, trachomatis,
more than 35 years- UTI, E. Coli, pseudomonas.
Vascular lesions
testicular torsion, twisting of spermatic cord, obstruction of venous drainage, venous congestion, infarct.
Male infertility
failure to conceive afer one year of regular coitus wihtou contraception- testicular failure, obstruction, genetic, endocrinopathy.
etiology- pretesticular- hypopituitarism, estrogen excess,
testicular- agonadism, atrophy, gemr cell aplasia. maturation arrest.
Post testicular- B/L obstruction, infections immotile cilia cyndrome.
clincal features- Semen analysis- volume- normal 2-4 ml
sperm count 30 million/ ml
Morphology 80% normal, motile.
U/S CT scan hormones, gonadotrophins, androgens, estrogens, testicular biopsy
Testicular tumors-
more common in white male as compared to asians and africans
Etiology- isochromosome i12p, crytorchidism, testicular dysgenesis(klinefelter’s syndrome, radiation.
germ cell tumor, sex cord tumor, lymphoma, sarcome, metastaic tumors.
Trimodal age districtuion- infant- teratomas and yolk sac. 15-30 years miexed germ cell tumor.
classification- seminoma, non seminoma, mixed germ cell.
- -minimally differentiated- embryonal carcimnoma
- -somatic differentiation- teratoma
- -trophoblastic differentiation, choriocarcinoma
- yolk sac differentiation.- yolk sac carcinoma.
- -mixed germ cell is any combination of the two.
clinical features- unilateral testicular mass, feeling of heaviness in scrotum, dull ache in the groin or abdomen, hydrocele, testicular pain, breast enlargement, metastatic disease in lymph nodes.
treatment is resection for non seminoma- chemo for seminoma, radiotherapy, biopsy can cause seeding. diagnosis with clincal picutre, and serum levels of AFP, and BHCG for diagnosis and monitoring.
Staging-
stage 1 tumor confined to testis
Stage 2 metastasis confined to retroperitoneal lymph nodes below the level of the diaphragm
Stage 3 metastasis beyond retroperitoneal lymph nodes.
Prognosis- seminoma- excellent with radiotherapy, spread through lymph
non seminoma- good prognosis with chemo. spread through blood vessels and lymphatics.
Seminoma
30% of GCTs, middle age, pure pattern, sheets of cells with fride egg + lymphocytic infiltrate.
Non seminoma
embryonal carcinoma- 3% pure more in mixed,
-teratoma- children (Benign)/ adult (Malignant)
yolk sac tumor (serum AFP) children/adult)
choriocarcinoma ( serum B-HCG) rare
Mixed germ cell tumor-
seminoma and non seminoma ill defined hemorrhagic mass, cystic solid.
Sex cord/ stromal tumors-
rare, leydig, sertoli, granulosa cells- benign
hypospadias/epispadias
abnormalities on ventral surface of penis/
abnormaliites on the dorsal surface
May be associated with failure of normal descent of testis, inguinal hernia, malformations of urinary tract, Urinary tract obstruction, recurrent infections, infertility.
Phimosis-
the orifice of the prepuse is too small to permit normal retraction, due to development anomalies or infection and scarring of the preputial ring
paraphimosis
when a phimotic prepuse is forcibly retracted over the glans penis, causing marked contriction and swelling. ( painful urethral constrctions, urinary tract infections.
Penile carcinoma in situ
Epidemiology max incidence between 40-70 years.
Bowen’s disease: solitary, shaft, plaque/scaly- associated visceral malignancies- progress to invasive squamous cell Ca.
Erythroplasia of queyrat- solitary or multiple, glans and prepuce, red patch, shiny plaque, progress to squamous cell carcinoma
Bowenoid papulosis- multple, shaft glans/foreskins, papular, doesn’t progress to invasive squamous cell carcinoma.
Penile squamous cell carcinoma
- rare in jews and muslims, due to circumcision, happens more in china. Carcinogens in smegmaHPV 16,18Cigarette smokingAll associated with HPV infection
Slow growing locally invasive tumor- Prognosis related to stage of the tumor. without metastasis to regional lymph nodes has 66% 5 year survival rate with metastasis 27% 5 year survival rate.
Scrotal lesions
hematocele- blood in tunica vaginalis due to trauma
hydrocele- accumulation of lfuid in tunica
-chylocele- accumulation of lymph in tunica
-varicoceleL dilatation of congested blood vessels in spermatic cord
Spermatocele- dilatation of epididymis with semen- therapy is surgical resection.
Scrotal cancers
chimney sweepers, coal tar, skin cancer.
